An emerging role for the lateral habenula in aggressive behavior

Abstract

Inter-male aggression is an essential component of social behavior in organisms from insects to humans. However, when expressed inappropriately, aggression poses significant threats to the mental and physical health of both the aggressor and the target. Inappropriate aggression is a common feature of numerous neuropsychiatric disorders in humans and has been hypothesized to result from the atypical activation of reward circuitry in response to social targets. The lateral habenula (LHb) has recently been identified as a major node of the classical reward circuitry and inhibits the release of dopamine from the midbrain to signal negative valence. Here, we discuss the evidence linking LHb function to aggression and its valence, arguing that strong LHb outputs to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN) are likely to play roles in aggression and its rewarding components. Future studies should aim to elucidate how various inputs and outputs of the LHb shape motivation and reward in the context of aggression.

Keywords: Aggression; Bullying; Mesolimbic dopamine circuit; Reward.

Figure 1

Whole brain input-output map of LHb circuitry. A. Inputs to the LHb. The LHb receives inputs from many forebrain structures, including mPFC, BF, and EPN. B. Outputs of the LHb. The majority of LHb projections target midbrain regions like the RMTg, DRN, and VTA. Abbreviations: BF, basal forebrain; DRN, dorsal raphe nucleus; EPN, entopeduncular nucleus; LH, lateral hypothalamus; mPFC. medial prefrontal cortex; RMTg, rostromedial tegmental nucleus; VTA, ventral tegmental area.

Figure 2

Input-output map of LHb microcircuitry. Principal neurons of the LHb are vGlut2-positive and target the DRN, VTA, and RMTg. They receive a variety of inputs consisting of multiple neurotransmitters and neuropeptides. GAD65-positive neurons are also present in the LHb, but it is unknown whether these neurons synapse locally, on downstream target regions, or both. Abbreviations: BF, basal forebrain; DRN, dorsal raphe nucleus; EPN, entopeduncular nucleus; LH, lateral hypothalamus; mPFC. medial prefrontal cortex; RMTg, rostromedial tegmental nucleus; VTA, ventral tegmental area.